尽管生物大分子是有前途的胞质药物，引起了极大的关注，但主要的障碍是细胞膜阻碍进入和内体截留导致生物大分子降解。如何避免这些限制来实现直接胞质递送仍然是一个挑战。在这里，我们制备了寡精氨酸修饰的脂质来组装用于生物大分子递送的纳米囊泡，包括mRNA（mRNA）和蛋白质，这些生物大分子可以通过亚内吞作用介导的膜融合直接递送到树突状细胞的细胞质中。我们将这种膜融合脂质纳米囊泡命名为MF-LNV。装载 MF-LNV 作为纳米疫苗的 mRNA 显示出有效的抗原表达，可引发癌症治疗的强大免疫反应。更重要的是，负载抗原蛋白的 MF-LNV 作为纳米疫苗，通过正常摄取途径，比脂质纳米颗粒能引发更强的 CD8 T 细胞特异性反应。这种 MF-LNV 代表了一种令人耳目一新的生物大分子细胞内递送策略。

Although biomacromolecules are promising cytosolic drugs which have attracted tremendous attention, the major obstacles were the cellular membrane hindering the entrance and the endosome entrapment inducing biomacromolecule degradation. How to avoid those limitations to realize directly cytosolic delivery was still a challenge. Here, we prepared oligoarginine modified lipid to assemble a nanovesicle for biomacromolecules delivery, including mRNA (mRNA) and proteins which could be directly delivered into the cytoplasm of dendritic cells through subendocytosis-mediated membrane fusion. We named this membrane fusion lipid nanovesicle as MF-LNV. The mRNA loaded MF-LNV as nanovaccines showed efficient antigen expression to elicit robust immuno responses for cancer therapy. What's more, the antigen protein loaded MF-LNV as nanovaccines elicits much stronger CD8+ T cell specific responses than lipid nanoparticles through normal uptake pathways. This MF-LNV represented a refreshing strategy for intracellular delivery of the biomacromolecule.